Eye health supplement with curcumin

ABSTRACT

An eye health supplement and methods of using the eye health supplement are disclosed.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of the earlier filing date of U.S.Provisional Application No. 62/786,270, filed Dec. 28, 2018, which isincorporated by reference in its entirety herein.

FIELD

This disclosure concerns embodiments of an eye health supplement dosageform and methods of use.

SUMMARY

Embodiments of an eye health supplement dosage form and methods of usingthe eye health supplement dosage form are disclosed.

In some embodiments, the eye health supplement dosage form includes 1part by weight zeaxanthin, 1-20 parts by weight lutein, 4-70 parts byweight vitamin E, 0.8-15 parts by weight zinc, 6-100 parts by weightcurcumin, and 6-100 parts by weight omega-3 oils providing 3-50 parts byweight docosahexaenoic acid (DHA) and 3-50 parts by weighteicosapentaenoic acid (EPA). In certain embodiments, the eye healthsupplement dosage form includes 1-4 mg zeaxanthin, 5-20 mg lutein,16.75-67 mg vitamin E, 3.75-15 mg zinc, 25-100 mg curcumin; and 25-100mg omega-3 oils comprising 12.5-50 mg DHA and 12.5-50 mg EPA.

In any of the above embodiments, the eye health supplement dosage formmay further comprise fish oil, gelatin, glycerin, sunflower oil, yellowbeeswax, water, carob, or any combination thereof. In some embodiments,the eye health supplement dosage form consists essentially of, orconsists of, zeaxanthin, lutein, vitamin E, zinc, curcumin, DHA, EPA,fish oil, glycerin, sunflower oil, yellow beeswax, water, and carob. Incertain embodiments, the eye health supplement dosage form consistsessentially of, or consists of, 2 mg zeaxanthin, 10 mg lutein, 33.5 mgvitamin E, 7.5 mg zinc, 50 mg curcumin; 25 mg DHA, 25 mg EPA, fish oil,gelatin, glycerin, sunflower oil, yellow beeswax, water, and carob.

In any of the above embodiments, the zinc may be provided by zincgluconate. In any of the above embodiments, the eye health supplementdosage form may not comprise resveratrol. In some embodiments, the eyehealth supplement dosage form is a softgel.

In some embodiments, a method of supporting eye health includesadministering to a subject a dose of an eye health supplement dosageform as disclosed herein, wherein the dose is effective to support eyehealth. Administering may be performed daily.

In some embodiments, the dose comprises 4 mg zeaxanthin, 20 mg lutein,67 mg vitamin E, 15 mg zinc, 100 mg curcumin, 50 mg DHA, and 50 mg EPA.In certain embodiments, administering comprises orally administering twoeye health supplement dosage forms to the subject, each eye healthsupplement dosage form comprising 2 mg zeaxanthin, 10 mg lutein, 33.5 mgvitamin E, 7.5 mg zinc, 50 mg curcumin, 25 mg DHA, and 25 mg EPA.

In any of the above embodiments, supporting eye health may comprisesupporting a healthy retina, supporting visual performance, or acombination thereof. Supporting a healthy retina may include supportinga macular pigment density of at least 0.60 over a period of time.Supporting visual performance may comprise any one or more of, or allof, (i) supporting visual processing speed, (ii) supporting the abilityof the subject's eyes to recover from glare, and/or (iii) supportingcontrast sensitivity.

DETAILED DESCRIPTION

A healthy retina, including the macula, is an important part of the eyefor vision throughout life. The retina, including the macula, isconstantly under stress. As they age, many people develop significantproblems that impact their vision.

Embodiments of the disclosed eye health supplement, when administered toa subject, support eye health. In some embodiments, the eye healthsupplement supports a healthy retina and/or visual performance. Incertain embodiments, the eye health supplement supports eye health of asubject exposed to blue light. For example, embodiments of the eyehealth supplement may support macular density (e.g., lutein andzeaxanthin pigment density), support visual performance in low lightconditions, support the ability of the subject's eyes to recover fromglare, and/or support contrast sensitivity.

I. Definitions and Abbreviations

The following explanations of terms and abbreviations are provided tobetter describe the present disclosure and to guide those of ordinaryskill in the art in the practice of the present disclosure. As usedherein, “comprising” means “including” and the singular forms “a” or“an” or “the” include plural references unless the context clearlydictates otherwise. The term “or” refers to a single element of statedalternative elements or a combination of two or more elements, unlessthe context clearly indicates otherwise. In addition, the term “and/or”when used in this document is to be construed to include the conjunctive“and”, the disjunctive “or”, and both “and” and “or”. Also, the terms“includes” and “has” have the same meaning as “comprises” and the terms“including” and “having” have the same meaning as “comprising”.

Unless explained otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood to one of ordinaryskill in the art to which this disclosure belongs. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present disclosure, suitable methods andmaterials are described below. The materials, methods, and examples areillustrative only and not intended to be limiting. Other features of thedisclosure are apparent from the following detailed description and theclaims.

The disclosure of numerical ranges should be understood as referring toeach discrete point within the range, inclusive of endpoints, unlessotherwise noted. Unless otherwise indicated, all numbers expressingquantities of components as used in the specification or claims are tobe understood as encompassing variations up to ±5% relative to thestated value. When the disclosure states “substantially equal to,” thefollowing value encompasses variations up to ±2% relative to the statedvalue. When the disclosure states “equal to,” the following valueencompasses variations up to ±1% relative to the stated value.

Although there are alternatives for various components, parameters,operating conditions, etc. set forth herein, that does not mean thatthose alternatives are necessarily equivalent and/or perform equallywell. Nor does it mean that the alternatives are listed in a preferredorder unless stated otherwise.

Definitions of common terms in chemistry may be found in Richard J.Lewis, Sr. (ed.), Hawley's Condensed Chemical Dictionary, published byJohn Wiley & Sons, Inc., 2016 (ISBN 978-1-118-13515-0).

In order to facilitate review of the various embodiments of thedisclosure, the following explanations of specific terms are provided:

Administering: Administration by any route to a subject (e.g., a human).As used herein, administration typically but not necessarily refers tooral administration.

Consisting essentially of: The term “consisting essentially of” meansthat the eye health supplement does not contain any active componentsother than those recited, and contains no more than trace amounts (e.g.,<1 wt %) of additional non-active components.

Consisting of: The term “consisting of” excludes all components notspecified except for impurities ordinarily associated therewith.

Curcumin: A compound produced by some plants, such as turmeric; alsoknown as(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione,diferuloylmethane, natural yellow 3, or turmeric yellow.

Dosage form: A form suitable for administration to a subject, e.g., asoftgel, tablet, capsule, or the like. The dosage forms of the claimscan be broken up into sub-dosage form which together comprise or consistessentially of the components that add up to the dosage form.

Effective dose: An amount sufficient to provide and/or support abeneficial effect to a subject or a given percentage of subjects.

Omega-3 oil: A polyunsaturated fatty acid characterized by a double bondthree atoms away from the terminal methyl group. The three primaryomega-3 oils in human physiology are α-linolenic acid (ALA),eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA isfound in plant oils. EPA and DHA are commonly found in marine oils andare obtained from fish, fish oils, squid oils, and krill oil.

Softgel: An oral dosage form, typically comprising a gelatin-based shellsurrounding a liquid fill.

Subject: As used herein, the term “subject” refers to a mammal,particularly a human.

Vitamin E: The term vitamin E, as used herein, is synonymous withd-alpha tocopherol. Vitamin E may be measured in milligrams orinternational units (IU), where 1 IU is the biological equivalent of0.67 mg d-alpha tocopherol.

II. Eye Health Supplement Dosage Form

Embodiments of the disclosed eye health supplement dosage form includezeaxanthin, lutein, vitamin E, zinc, curcumin, and omega-3 oils, theomega-3 oils providing docosaheaenoic acid (DHA) and eicosapentaenoicacid (EPA). The zinc may be provided by zinc gluconate. In someembodiments, the eye health supplement dosage form does not compriseresveratrol.

In any of the above embodiments, the eye health supplement dosage formmay comprise 1 part by weight zeaxanthin, 1-20 parts by weight lutein,4-70 parts by weight vitamin E, 0.8-15 parts by weight zinc, 6-100 partsby weight curcumin, and 6-100 parts by weight omega-3 oils providing3-50 parts by weight docosahexaenoic acid (DHA) and 3-50 parts by weighteicosapentaenoic acid (EPA). In one embodiment, the eye healthsupplement dosage form comprises 1 part by weight zeaxanthin, 1-15 partsby weight lutein, 4-50 parts by weight vitamin E, 1-10 parts by weightzinc, 10-50 parts by weight curcumin, and 10-50 parts by weight omega-3oils providing 5-25 parts by weight docosahexaenoic acid DHA and 5-25parts by weight EPA. In another embodiment, the eye health supplementdosage form comprises 1 part by weight zeaxanthin, 1-10 parts by weightlutein, 10-25 parts by weight vitamin E, 1-5 parts by weight zinc, 20-30parts by weight curcumin, and 20-30 parts by weight omega-3 oilsproviding 10-15 parts by weight docosahexaenoic acid DHA and 10-15 partsby weight EPA. In still another embodiment, the eye health supplementdosage form comprises 1 part by weight zeaxanthin, 5 parts by weightlutein, 16.75 parts by weight vitamin E, 3.75 parts by weight zinc, 25parts by weight curcumin, and 25 parts by weight omega-3 oils providing12.5 parts by weight docosahexaenoic acid DHA and 12.5 parts by weightEPA. In yet another embodiment, the eye health supplement dosage formcomprises the following components in amounts substantially equal to, orequal to, 1 part by weight zeaxanthin, 5 parts by weight lutein, 16.75parts by weight vitamin E, 3.75 parts by weight zinc, 25 parts by weightcurcumin, and 25 parts by weight omega-3 oils providing 12.5 parts byweight docosahexaenoic acid DHA and 12.5 parts by weight EPA.

In any of the above embodiments, the eye health supplement dosage formmay comprise 1-4 mg zeaxanthin, 5-20 mg lutein, 16.75-67 mg vitamin E,3.75-15 mg zinc, 25-100 mg curcumin; and 25-100 mg omega-3 oilscomprising 12.5-50 mg DHA and 12.5-50 mg EPA. In one embodiment, the eyehealth supplement dosage form comprises 1-3 mg zeaxanthin, 8-12 mglutein, 25-40 mg vitamin E, 5-10 mg zinc, 40-60 mg curcumin; and 40-60mg omega-3 oils comprising 20-30 mg DHA and 20-30 mg EPA. In anotherembodiment, the eye health supplement dosage form comprises 2 mgzeaxanthin, 10 mg lutein, 33.5 mg vitamin E, 7.5 mg zinc, 50 mgcurcumin; 25 mg DHA and 25 mg EPA. In some examples, the amounts aresubstantially equal to, or equal to, 2 mg zeaxanthin, 10 mg lutein, 33.5mg vitamin E, 7.5 mg zinc, 50 mg curcumin; 25 mg DHA and 25 mg EPA.

In any of the above embodiments, the eye health supplement dosage formmay further comprise fish oil, gelatin, glycerin, sunflower oil, yellowbeeswax, water, carob, or any combination thereof. In some embodiments,the eye health supplement dosage form consists essentially of, orconsists of, zeaxanthin, lutein, vitamin E, zinc, curcumin, DHA, EPA,fish oil, glycerin, sunflower oil, yellow beeswax, water, and carob. Incertain embodiments, the eye health supplement dosage form consistsessentially of, or consists of, 2 mg zeaxanthin, 10 mg lutein, 33.5 mgvitamin E, 7.5 mg zinc, 50 mg curcumin; 25 mg DHA, 25 mg EPA, fish oil,gelatin, glycerin, sunflower oil, yellow beeswax, water, and carob. Incertain embodiments, the eye health supplement dosage form consistsessentially of, or consists of, the following components in amountssubstantially equal to, or equal to, 2 mg zeaxanthin, 10 mg lutein, 33.5mg vitamin E, 7.5 mg zinc, 50 mg curcumin; 25 mg DHA, 25 mg EPA, plusfish oil, gelatin, glycerin, sunflower oil, yellow beeswax, water, andcarob.

In any of the foregoing embodiments, the zinc may be provided by zincgluconate. In any of the foregoing embodiments, the lutein may bepresent as free lutein. In some embodiments, the lutein and zeaxanthinare provided by Lutemax 2020® marigold extract (OmniActive HealthTechnologies, Morristown, N.J.), an extract providing lutein and bothzeaxanthin isomers (R,R and R,S [meso]-zeaxanthin) at a 5:1 ratio bymass.

In any of the foregoing embodiments, the dosage form may be a softgel, acapsule (e.g., a sealed hard capsule), or a tablet. In some embodiments,the dosage form is a softgel. Softgels typically comprise agelatin-based shell surrounding a liquid fill. Thus, in someembodiments, the dosage form comprises a gelatin-based shell surroundinga liquid fill comprising, consisting essentially of, or consisting ofzeaxanthin, lutein, vitamin E, zinc, curcumin, DHA, EPA, fish oil,glycerin, sunflower oil, yellow beeswax, water, and carob. Thegelatin-based shell may comprise gelatin, water, a plasticizer, andoptionally an opacifier and/or a colorant.

III. Methods of Use

Embodiments of a method for supporting eye health comprise administeringto a subject a dose of an eye health supplement dosage form as disclosedherein, wherein the dose is effective to support eye health. In someembodiments, the effective dose comprises 2-8 mg zeaxanthin, 10-40 mglutein, 33.5-134 mg vitamin E, 7.5-30 mg zinc, 50-200 mg curcumin; and50-200 mg omega-3 oils comprising 25-100 mg DHA and 25-100 mg EPA. Inone embodiment, the effective dose comprises 3-5 mg zeaxanthin, 15-25 mglutein, 50-76 mg vitamin E, 10-20 mg zinc, 72-125 mg curcumin; and80-120 mg omega-3 oils comprising 40-60 mg DHA and 40-60 mg EPA. Inanother embodiment, the effective dose comprises 4 mg zeaxanthin, 20 mglutein, 67 mg vitamin E, 15 mg zinc, 100 mg curcumin, 50 mg DHA, and 50mg EPA. In another embodiment, the effective dose comprises thefollowing components in amounts substantially equal to, or equal to, 4mg zeaxanthin, 20 mg lutein, 67 mg vitamin E, 15 mg zinc, 100 mgcurcumin, 50 mg DHA, and 50 mg EPA. In any of the foregoing embodiments,the zinc may be provided by zinc gluconate.

Administration may be by any suitable route, although in most instancesthe dosage form is orally administered. In some embodiments, the dose isadministered daily. The dose may be administered once daily, or the dosemay be broken into two or more sub-doses administered throughout theday. For example, one half of the dose may be administered at a firsttime and the second half of the dose may be administered at a subsequenttime.

In some embodiments, each dosage form includes less than the effectivedose, and more than one dosage form can be taken by the subject. Forexample, in certain embodiments, each dosage form includes half of theeffective dosage, and the subject takes two dosage forms in a day. Insuch embodiments, each eye health supplement dosage form comprises 1-4mg zeaxanthin, 5-20 mg lutein, 16.75-134 mg vitamin E, 3.75-15 mg zinc,25-100 mg curcumin; and 25-100 mg omega-3 oils comprising 12.5-50 mg DHAand 12.5-50 mg EPA. In certain embodiments, each eye health supplementdosage form comprises 2 mg zeaxanthin, 10 mg lutein, 33.5 mg vitamin E,7.5 mg zinc, 50 mg curcumin, 25 mg DHA, and 25 mg EPA. In certainembodiments, administering comprises orally administering two eye healthsupplement dosage forms to the subject, each eye health supplementdosage form comprising 2 mg zeaxanthin, 10 mg lutein, 33.5 mg vitamin E,7.5 mg zinc, 50 mg curcumin, 25 mg DHA, and 25 mg EPA. In some examples,the amounts are substantially equal to, or equal to, 2 mg zeaxanthin, 10mg lutein, 33.5 mg vitamin E, 7.5 mg zinc, 50 mg curcumin, 25 mg DHA,and 25 mg EPA. In any of the foregoing embodiments, the zinc may beprovided by zinc gluconate.

Zeaxanthin and lutein can be obtained from dietary sources, such asdark-green leafy vegetables, eggs, carrots, sweet potatoes, dried fruit,citrus fruit, green peas, green beans, romaine lettuce, Brussel sprouts,bell peppers, grapes, squash, and corn. However, zeaxanthin and luteinsupplementation has been shown to exhibit a beneficial effect on ocularhealth, particularly as a subject ages. Zeaxanthin and lutein arepresent in the macula and supplementation may support or even increasemacular pigment optical density and/or promote enhanced visual healthand performance, which is indicative of good retinal health. A thirdcarotenoid, meso-zeaxanthin is a non-dietary carotenoid that is alsopresent in the macula. Meso-zeaxanthin is produced in the retina fromlutein by isomerization. Zeaxanthin and lutein supplementation also beenshown to increase visual processing speed as macular pigment density isaugmented. Zeaxanthin and lutein supplementation also has been shown toimprove visual recovery from glare and to improve visual performance inlow light. These features may be attributed at least in part to thespectral properties of zeaxanthin and lutein, which absorbshort-wavelength (blue) light (e.g., light having a wavelength within arange of 380-550 nm). Additionally, zeaxanthin and luteinsupplementation has been correlated with a reduced risk of age-relatedmacular degeneration (AMD).

Omega-3 oils, particularly DHA and EPA, enhance the bioavailability oflutein and zeaxanthin, as well as the bioavailability of vitamin E. DHAalso provides essential structural components of the retina. Vitamin E,DHA, and lutein have been shown to work in concert by aggregatingtogether in neural membranes, and interacting to promote healthy tissueand function.

Zinc plays a role in maintaining normal ocular function, and is presentin high concentrations in ocular tissue, particularly in the retina andchoroid. Curcumin is the main component of the spice turmeric (Curcumalonga). Curcumin has an appreciable anti-inflammatory effect in the eye,thereby supporting eye health.

Researchers with the Age-Related Eye Disease Study (AREDS) reported in2001 that a formulation including 500 mg vitamin C, 400 internationalunits of vitamin E, 15 mg beta-carotene, 80 mg zinc as zinc oxide, and 2mg copper as cupric oxide could reduce the risk of developing advancedage-related macular degeneration (AMD). In 2006, the original AREDSformulation was modified to omit beta-carotene, and add 10 mg lutein, 2mg zeaxanthin, and 1000 mg of omega-3 fatty acids (350 mg DHA and 650 mgEPA. The revised formulation is known as AREDS2.

In some embodiments, a dose of the eye health supplement dosage formdisclosed herein includes greater amounts of zeaxanthin and/or luteinthan a dose of the AREDS2 formulation. For example, where a dose of theAREDS2 formulation includes 2 mg zeaxanthin and 10 mg lutein, a dose ofthe disclosed eye health supplement dosage form may include 4 mgzeaxanthin and 20 mg lutein, thereby providing superior results insupporting eye health. The superior results may be more pronounced inolder subjects, such as subjects over the age of 30, over the age of 40over the age of 50, or over the age of 60. Older subjects may experiencereduced bioavailability of zeaxanthin and/or lutein from supplements,resulting in decreased absorption in the subject's serum and/or eye.

In some embodiments, administering to a subject a dose of an eye healthsupplement dosage form as disclosed herein supports eye health.Supporting eye health may comprise supporting a healthy retina,supporting visual performance, or a combination thereof.

Supporting a healthy retina includes supporting macular density over aperiod of time, such as a period of several days, weeks, months, or evenyears. Macular density refers to macular pigment density. Macularpigment is a pigmented spot in the center of the retina. The macularpigment comprises lutein and zeaxanthin. The macular pigment protectsthe macula from harmful blue light and helps maintain macular function.The thickness or density of the macular pigment varies amongstindividuals and can change over time. In particular, macular pigmentdensity may decrease as a subject ages. Low macular density is a knownrisk factor for AMD. A low macular density also may reduce visualprocessing speed. Studies have shown that macular density also isrelated to glare disability and photostress recovery (Stringham et al.,Optom Vis Sci 2008, 85:82-88). Macular pigment optical density (MPOD)may be measured, for example, using dual wavelength autofluorescenceimaging, scanning laser ophthalmoscopy, resonance Raman spectroscopy, orheterochromatic flicker photometry technology. The MPOD score is basedon a scale from 0 to 1. A low MPOD score may be defined as a score offrom 0-0.2, a mid-range is an MPOD score from 0.21-0.44, and an MPODscore greater than 0.45 is considered to be a high density. A scorebelow 0.45 indicates an increased risk of developing AMD. Based onvisual performance data, an MPOD of at least 0.60 is desirable(Stringham et al., ARVO Meeting Abstracts Apr. 22, 2011, 52:3638). Somestudies have shown that MPOD may peak at 45-50 years of age, followed bya gradual decrease as a subject ages, particular after the age of 60(see, e.g., Lima et al., Clinical Ophthalmology 2013, 7:685-690).Stringham et al. demonstrated that MPOD may be increased with lutein andzeaxanthin supplementation (Stringham et al., Optom Vis Sci 2008,85:82-88). Effects of curcumin may be assessed, at least in part, bymeasuring serum inflammatory cytokine levels (e.g., IL-6, TNF-α, andIL-1β), by a suitable method such as enzyme-linked immunosorbent assay(ELISA).

Supporting visual performance may include (i) supporting visualprocessing speed, (ii) supporting the ability of the subject's eyes torecover from glare, (iii) supporting contrast sensitivity, or (iv) anycombination of (i), (ii), and (iii). In some embodiments, the eye healthsupplemental dosage form is administered to a subject who is exposed toblue light. Even in the absence of ocular disease, many older adultshave difficulty seeing under low illumination including a loss ofsteady-state light sensitivity and a delay in rod-mediated darkadaptation; older adults also may experience delayed glare recovery(see, e.g., Owsley, Annu Rev Vis Sci 2016, 2:255-271; Babizhayev,Ophthalmic Res 2003, 35:19-25; Haegerstrom-Portnoy et al., Optometry andVis Sci 1999, 76(3):141-158). Low luminance visual acuity may beassessed, for example, with a SKILL card (Haegerstrom-Portnoy et al.,Invest. Ophthalmol Vis Sci 1997, 38:207-218). Glare recovery may beassessed, for example, having a subject view the glare source of theBerkley Glare test (Bailey, Optom Vis Sci 1991, 68:911-917) for oneminute, followed by assessing visual acuity based on the time requiredfor the subject to read the line two lines larger than the subject'spreviously assessed SKILL dark chart acuity (Haegerstrom-Portnoy et al.,Optometry and Vis Sci 1999, 76(3):141-158). Photostress, or glarerecovery, and/or contrast sensitivity also may be assessed with an 8cycle/degree, 15% contrast Gabor patch target after each of fivesuccessive exposures to intense LED lights (Stringham et al., Eye andVision 2016 3:30). Stringham et al. demonstrated that MPOD may beincreased with lutein and zeaxanthin supplementation, with concomitantimprovements in disability glare threshold and photostress recovery(Stringham et al., Optom Vis Sci 2008, 85:82-88; Stringham et al., Eyeand Vision 2016 3:30). Visual processing speed may be assessed bydetermining the critical flicker fusion threshold (Hammond et al.,Ophthalmic Physiol Opt 2005, 25(4):315-319).

In some embodiments, administering to a subject a dose of an eye healthsupplement dosage form as disclosed herein, particularly when thesubject is administered doses of the eye health supplement dosage formover a period of time, supports a healthy retina, e.g., by supportingmacular density. For example, the macular density may remainsubstantially stable (e.g., varying by less than 10% relative to aninitial macular pigment density) over a period of days, weeks, months,or years, or may decrease at a slower rate compared to the maculardensity of a subject that has not been administered the eye healthsupplement dosage form or compared to a rate of macular density decreasein the subject prior to receiving the eye health supplement dosage form.

In some embodiments, administering to a subject a dose of an eye healthsupplement dosage form as disclosed herein, particularly when thesubject is administered doses of the eye health supplement dosage formover a period of time, supports visual performance. A subject receivingdoses of the eye health supplement dosage form, particularly over aperiod of several days, weeks, months, or years, may experience greaterand/or more stable visual performance, as evidenced by increased visualacuity and/or decreased eye discomfort, in low-light conditions such asin dimly-lit areas or at nighttime, relative to the subject's visualperformance prior to receiving the eye health supplement dosage form orcompared to a similar subject (e.g., similar age, same gender, similargeneral health) did not receive the eye health supplement dosage form.Alternatively, the subject's visual performance in low-light conditionsmay show greater stability over a period of days, weeks, months, oryears, compared to a similar subject who did not receive the eye healthsupplement dosage form or relative to the subject's own visualperformance prior to receiving the eye health supplement dosage form. Asubject receiving doses of the eye health supplement dosage form,particularly over a period of several days, weeks, months, or years,also may report an increased ability of the eyes to recover from glare,such as glare attributable to blue light, relative to the subject'sability to recover from glare prior to receiving the eye healthsupplement dosage form.

Advantageously, the increased amounts of zeaxanthin and lutein presentin the disclosed eye health supplement dosage forms relative to theAREDS2 formulation may provide faster and/or enhanced benefits to thesubject, such as a more stable macular pigment density, a greaterincrease in macular pigment density, a more stable visual processingspeed, improved visual processing speed, a more stable contrastsensitivity, an improved contrast sensitivity, a more stable ability torecover from glare, and/or an increased ability to recover from glare,compared to a similar subject that receives the AREDS2 formulation or toa similar subject that does not receive an eye health supplement. Thesubject also may experience a more stable or increased macular pigmentdensity and/or a more stable or improved visual performance relative tothe subject's own macular pigment density and/or visual performanceprior to receiving one or more doses of the disclosed eye healthsupplement dosage forms.

IV. Methods of Making

Methods of making softgel, hard capsule, and tablet dosage forms areknown in the art. Processes for making softgel capsule shells, hardcapsules, and tablets are known. See, e.g., Aulton, M., Aulton'sPharmaceutics: The Design & Manufacture of Medicines, 527-533 (Kevin M GTaylor, Ed., 3rd Ed., 2001). In some embodiments, the dosage form is asoftgel made by a rotary die process involving continuous formation of aheat seal between two ribbons of gelatin to form a soft capsule shellwhile simultaneously filling the shell with a fill formulation. Thegelatin composition for the shell may further include a plasticizer(e.g., glycerol, sorbitol, propylene glycol, or the like) and/or acolorant. In certain embodiments, the process of making the softgel mayfurther include applying a coating to the softgel. For example, anenteric coating may be applied to a softgel as is known to those skilledin the art.

Typically, the fill formulation is a liquid at the manufacturingtemperature. The fill formulation comprises zeaxanthin, lutein, vitaminE, zinc, curcumin, and omega-3 oils, the omega-3 oils providingdocosaheaenoic acid (DHA) and eicosapentaenoic acid (EPA). In someembodiments, the fill formulation comprises, consists essentially of, orconsists of, zeaxanthin, lutein, vitamin E, zinc, curcumin, omega-3 oilscomprising DHA and EPA, fish oil, glycerin, sunflower oil, yellowbeeswax, water, and carob.

V. Examples Example 1 Effects of Xanthophyll Supplementation with andwithout Curcumin on Inflammation, Visual Performance, Eye Strain, andEye Fatigue

The purpose of this proposed study is to determine effects of an eyehealth supplement containing lutein, zeaxanthin, EPA, and DHA, but withor without 100 mg of curcumin. Outcomes to be addressed include macularpigment optical density (MPOD), visual processing speed, inflammatorycytokine levels (e.g., IL-6, TNF-α, and IL-1β) and contrast sensitivity.

Methods: Healthy adults (e.g., adults aged 25-49 yrs.) will be recruitedto participate in this placebo-controlled comparison trial. The placebogroup will ingest daily a pill that contains only sunflower oil. Thetreatment groups will be asked to ingest daily a pill containing 24 mgof lutein and zeaxanthin, 150 mg of EPA/DHA, and either no curcumin or100 mg curcumin. Measures of eye strain and eye fatigue will be assessedvia questionnaire. MPOD will be assessed via heterochromatic flickerphotometry. Serum inflammatory parameters will be assessed viaenzyme-linked immunosorbent assay (ELISA).

Results: It is expected that, at baseline, MPOD will be correlatedsignificantly with all visual performance measures. In terms of theintervention, it is expected that those in the curcumin group willexhibit similar results in terms of visual performance and MPODaugmentation as the other nutrient supplementation group, but havesignificantly lower serum inflammatory levels, and perhaps report lowereye strain and eye fatigue. We also expect that both treatment groupswill improve significantly for all parameters versus placebo.

In view of the many possible embodiments to which the principles of thedisclosed invention may be applied, it should be recognized that theillustrated embodiments, as described in the claims, which form aportion of this disclosure, are only desirable examples of the inventionand should not be taken as limiting the scope of the invention. Rather,the scope of the invention is defined by the following claims, which areincorporated into this specification and form a portion of thisdisclosure. I therefore claim as my invention all that comes within thescope and spirit of these claims.

I claim:
 1. An eye health supplement dosage form, comprising: at least 6mg zeaxanthin; at least 30 mg lutein; 16.75-67 mg vitamin E; 3.75-15 mgzinc; 25-100 mg curcumin; and 25-100 mg omega-3 oils providing 12.5-50mg docosahexaenoic acid (DHA) and 12.5-50 mg eicosapentaenoic acid(EPA), wherein the zinc is provided by zinc gluconate.
 2. The eye healthsupplement dosage form of claim 1, wherein the eye health supplementdosage form does not comprise resveratrol.
 3. The eye health supplementdosage form of claim 1, comprising: 1 part by weight zeaxanthin; 5 partsby weight lutein; 16.75 parts by weight vitamin E; 3.75 parts by weightzinc; 25 parts by weight curcumin; and 25 parts by weight omega-3 oilsproviding 12.5 parts by weight DHA and 12.5 parts by weight EPA.
 4. Theeye health supplement dosage form of claim 1, further comprising fishoil, gelatin, sunflower oil, glycerin, yellow beeswax, water, carob, orany combination thereof.
 5. The eye health supplement dosage form ofclaim 1, wherein the lutein is present as free lutein.
 6. The eye healthsupplement dosage form of claim 1, wherein the dosage form is a softgel.7. A method of supporting eye health, comprising administering to asubject a dose of an eye health supplement dosage form according toclaim 1, wherein the dose is effective to support eye health.
 8. Themethod of claim 7, wherein administering is performed daily.
 9. Themethod of claim 7, wherein the dose comprises 4 mg zeaxanthin, 20 mglutein, 67 mg vitamin E, 15 mg zinc, 100 mg curcumin, 50 mg DHA, and 50mg EPA.
 10. The method of claim 9, wherein the amounts are substantiallyequal to 4 mg zeaxanthin, 20 mg lutein, 67 mg vitamin E, 15 mg zinc, 100mg curcumin, 50 mg DHA, and 50 mg EPA.
 11. The method of claim 7,wherein administering comprises orally administering two eye healthsupplement dosage forms to the subject, each eye health supplementdosage form comprising 2 mg zeaxanthin, 10 mg lutein, 33.5 mg vitamin E,7.5 mg zinc, 50 mg curcumin, 25 mg DHA, and 25 mg EPA.
 12. The method ofclaim 11, wherein the amounts are substantially equal to 2 mgzeaxanthin, 10 mg lutein, 33.5 mg vitamin E, 7.5 mg zinc, 50 mgcurcumin, 25 mg DHA, and 25 mg EPA.
 13. The method of claim 7, whereinthe subject is exposed to blue light.
 14. The method of claim 7, whereinsupporting eye health comprises supporting a healthy retina, supportingvisual performance; or a combination thereof.
 15. The method of claim14, wherein supporting a healthy retina comprises supporting a maculardensity of at least 0.60 over a period of time.
 16. The method of claim14, wherein supporting visual performance comprises (i) supportingvisual processing speed, (ii) supporting the ability of the subject'seyes to recover from glare, (iii) supporting contrast sensitivity, or(iv) any combination of (i), (ii), and (iii).